Neuroendocrine tumors of midgut and hindgut origin: tumor-node-metastasis classification determines clinical outcome

Cancer. 2011 Aug 1;117(15):3332-41. doi: 10.1002/cncr.25855. Epub 2011 Jan 18.


Background: Prognostic classification of neuroendocrine tumor (NET) patients is difficult due to the complexity of current classification systems. A recent proposal for a tumor-node-metastasis (TNM) classification and a grading system based on the proliferative fraction proved valid in NETs of foregut origin. The purpose of this study was to test the efficacy of a proposal for TNM staging and grading for midgut and hindgut NETs.

Methods: Two hundred seventy patients with histologically proven midgut and hindgut NETs were investigated. Epidemiological, clinicopathological, and tumor-specific data at initial diagnosis were recorded. Tumors were classified according to the World Health Organization (WHO) and the recent European Neuroendocrine Tumor Society-TNM staging and grading proposal. Survival analysis and statistical testing for independent prognostic factors were performed using log-rank tests and Cox regression.

Results: Of 270 NETs originating in the midgut or hindgut, 7% (5-year survival rate [YSR], 100%) were stage 1, 8% (5-YSR, 100%) were stage 2, 19% (5-YSR, 89.5%) were stage 3, and 66% (5-YSR, 83.3%) were stage 4 NETs; 62% (5-YSR 95.2%) were grade 1, 32% (5-YSR 82.0%) were grade 2, and 6% (5-YSR, 51.4%) were grade 3 NETs. WHO classification significantly separated poorly from well-differentiated NET or carcinomas but did not further discriminate. TNM staging significantly separated stages 1, 2, and 3 from stage 4 NETs, as did grading according to proliferative capacity for all grades. Multivariate analysis confirmed these results, particularly for Ki67 grading.

Conclusions: The acquired data confirmed the prognostic relevance of the proposed TNM staging and grading system and demonstrated the applicability of these classification tools. The TNM system can therefore facilitate therapeutic stratification and comparison of data from different institutions.

MeSH terms

  • Female
  • Humans
  • Intestinal Neoplasms / pathology*
  • Lymphatic Metastasis*
  • Male
  • Neuroendocrine Tumors / pathology*
  • Regression Analysis
  • Retrospective Studies
  • Survival Analysis
  • Treatment Outcome*